Advanced Organic

Chemistry
Chapter_1_PART B
MSC Students
Dima Sabbah, Ph.D.
Fall 2014
 Oxidation and Reduction
Introduction:
• Oxidation results in an increase in the number of bonds
between C and a more electronegative atom, C—Z, (usually
C—O) or decrease in the number of C—H bonds.
• Reduction results in a decrease in the number of C—Z bonds
(usually C—O) or an increase in the number of
C—H bonds.
Figure 12.1 A general scheme for the oxidation
and reduction of a carbon compound

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 Oxidation and Reduction
Introduction:
• Two carbon atoms may be involved in a single oxidation or
reduction reaction.
• The conversion of an alkyne to an alkene, or an alkene to an
alkane are examples of this type reduction because each
process adds two new C—H bonds to the starting material.

Figure 12.2 Oxidation

and reduction of
hydrocarbons

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 Oxidation and Reduction
Reducing Agents:
• There are three ways of introducing 2 Hs in a reduction.
1. The first method uses H2 gas. Catalytic hydrogenation
requires a metal catalyst (usually Pt, Pd or Ni) with H 2.
2. A second method adds two protons and two electrons to a
substrate, and 2H+ + 2e- = H2
➢Reductions of this sort use alkali metals as a source of
electrons, and liquid ammonia as a source of protons,
Nao in NH3 (liq) or Lio in NH3 (liq).
➢These are called dissolving metal reductions.

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 Oxidation and Reduction
Reducing Agents:
3. The third way is to add hydride (H¯) and a proton (H+).
➢The most common hydride reducing agents contain a
hydrogen atom bonded to boron or aluminum. Simple
examples include sodium borohydride (NaBH4) and
lithium aluminum hydride (LiAlH4).
➢NaBH4 and LiAlH4 deliver H¯ to the substrate, and then
a proton is added from H2O or an alcohol.

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 Oxidation and Reduction
Reduction of Alkenes: Catalytic Hydrogenation

• The addition of H2 occurs only in the presence of a metal catalyst,

and thus it is called catalytic hydrogenation.
• The catalyst consists of a metal, usually Pd, Pt, or Ni, adsorbed
onto a finely divided inert solid, such as charcoal.
• H2 adds in a syn fashion.

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 Oxidation and Reduction
Reduction of Alkenes: Catalytic Hydrogenation
• The Ho of hydrogenation, also known as the heat of hydrogenation,
can be used as a measure of the relative stability of two different
alkenes that are hydrogenated to form the same alkane.

• When hydrogenation of two alkenes gives the same alkane, the

more stable alkene has the smaller heat of hydrogenation. 7
 Oxidation and Reduction
Reduction of Alkenes: Catalytic Hydrogenation

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 Oxidation and Reduction
Reduction of Alkenes: Catalytic Hydrogenation
• The mechanism explains two facts about hydrogenation:

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 Oxidation and Reduction
Reduction of Alkenes: Catalytic Hydrogenation
• When unsaturated vegetable oil is treated with hydrogen, some or all
of the  bonds add H2. This increases the melting point of the oil.
• Margarine is prepared by partially hydrogenating vegetable oils to give
a product with a consistency that more closely resembles butter.

Figure 12.4 Partial

hydrogenation of
the double bonds
in a vegetable oil 10
 Oxidation and Reduction
Reduction of Alkynes:
• There are three paths to add H2 to a triple bond:

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 Oxidation and Reduction
Alkyne reduction to an Alkane:
Alkane formation from two successive additions:

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 Oxidation and Reduction
Alkyne reduction to a Cis Alkene:
• Palladium metal is too reactive to allow hydrogenation of an
alkyne to stop after one equivalent of H2 adds.
• To stop at a cis alkene, a less active Pd catalyst is used, Pd
adsorbed onto CaCO3 with added lead(II) acetate and
quinoline. This is called Lindlar’s catalyst.
• Compared to Pd metal, the Lindlar catalyst is deactivated or
“poisoned”.
• With the Lindlar catalyst, one equivalent of H2 adds to an
alkyne to form the cis product. The cis alkene product is
unreactive to further reduction.

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 Oxidation and Reduction
Alkyne reduction to a Cis Alkene:

• Reduction of an alkyne to a cis alkene is a stereoselective

reaction, because only one stereoisomer is formed.
• Remember, one can also use hydroboration-acidification
instead of Lindlar’s catalyst to get a cis alkene.

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 Oxidation and Reduction
Alkyne reduction to a Trans Alkene:
• Dissolving metal reduction of a triple bond with Na in NH 3 is a
stereoselective reaction because it forms a trans product
exclusively.
• Dissolving metal reductions always form the more stable trans
product preferentially.
• The trans alkene is formed because the vinyl carbanion
intermediate that is formed is more stable when the larger R
groups are further away from each other to avoid steric
interactions. Protonation of this anion leads to the more stable
trans adduct.

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 Oxidation and Reduction
Alkyne reduction to a Trans Alkene:

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 Oxidation and Reduction
Alkyne reduction to a Trans Alkene:
• In a dissolving metal reduction (such as Na in NH3), the
elements of H2 are added in an anti fashion to form a trans
alkene. Na has only one electron, so, electrons for the
reduction are added sequentially from 2 Na atoms.

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 Oxidation and Reduction
Summary of Alkyne Reductions:
Figure 12.5 Summary: Three methods to reduce a triple bond

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 Oxidation and Reduction
Reduction of Polar C—X  Bonds:
• Alkyl halides can be reduced to alkanes with LiAlH4.
• Epoxide rings can be opened with LiAlH4 to form alcohols.

Figure 12.6 Examples

of reduction of C – X
σ bonds with LiAIH4

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 Oxidation and Reduction

Reduction of Polar C—X  Bonds:

• This reaction follows an SN2 mechanism.

• Unhindered CH3X and 1° alkyl halides are more easily reduced
than more substituted 2° and 3° halides.
• In unsymmetrical epoxides, nucleophilic attack of H¯ (from LiAlH4)
occurs at the less substituted carbon atom.
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 Oxidation and Reduction
Oxidizing Agents:
• There are two main categories of oxidizing agents:
1. Reagents that contain an oxygen-oxygen bond
2. Reagents that contain metal-oxygen bonds
• Oxidizing agents containing an O—O bond include O2, O3
(ozone), H2O2 (hydrogen peroxide), (CH3)3COOH (tert-
butyl hydroperoxide), and peroxyacids.
• Peroxyacids (or peracids) have the general formula
RCO3H.

Figure 12.7
Common
peroxyacids

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 Oxidation and Reduction
Oxidizing Agents:
• The most common oxidizing agents with metal-oxygen bonds
contain either chromium +6 (six Cr—O bonds) or manganese +7
(seven Mn—O bonds).
• Common Cr6+ reagents include CrO3 and sodium or potassium
dichromate (Na2Cr2O7 and K2Cr2O7). Pyridinium chlorochromate
(PCC) is a more selective Cr6+ oxidant.

• The most common Mn7+ reagent is KMnO4 (potassium

permanganate).
• Other oxidizing agents that contain metals include OsO 4 (osmium
22
tetroxide) and Ag2O [silver(I) oxide].
 Oxidation and Reduction

Oxidizing Agents:

Figure 12.8 Oxidation reactions of alkenes, alkynes, and alcohols

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 Oxidation and Reduction
Epoxidation:
• Epoxidation is the addition of a single oxygen atom to an alkene
to form an epoxide.
• Epoxidation is typically carried out with a peroxyacid.

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 Oxidation and Reduction
Epoxidation:
• Epoxidation occurs via syn addition of an O atom to either
side of a planar double bond. Thus, a cis alkene gives an
epoxide with cis substituents. A trans alkene gives an
epoxide with trans substituents.

• Epoxidation is stereospecific because cis and trans

alkenes yield different stereoisomers as products.
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 Oxidation and Reduction
Dihydroxylation:
• Dihydroxylation is the addition of two hydroxy groups to a
double bond, forming a 1,2-diol or glycol.
• Depending on the reagent, the two new OH groups can be
added to the opposite sides (anti addition) or the same side
(syn addition) of the double bond.

26
 Oxidation and Reduction
Anti-Dihydroxylation via an epoxide:
• Anti dihydroxylation is achieved in two steps: epoxidation,
followed by ring opening with ¯OH or H3O+.

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 Oxidation and Reduction

Syn Dihydroxylation:

• Syn hydroxylation results when an alkene is treated with

either KMnO4 or OsO4.

dilute

• The reaction of an alkene or an alkyne with dilute

KMnO4 is the Baeyer test for unsaturation. KMnO4 and
the MnO2 product is a brown precipitate.
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 Oxidation and Reduction
Syn Dihydroxylation:
• Each reagent adds two oxygen atoms in a syn fashion.
• Hydrolysis of the cyclic intermediate cleaves the metal oxygen
bonds, forming a cis-1,2-diol.

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 Oxidation and Reduction
Syn Dihydroxylation:
• Dihydroxylation can also be carried out by using a catalytic
amount of OsO4, if either the oxidant N-methylmorpholine N-oxide
(NMO) or hydrogen peroxide is also added.
• In the catalytic process, dihydroxylation of the double bond
converts the Os8+ oxidant into an Os6+ product, which is then
reoxidized by NMO or H2O2 to Os8+.

or H2O2

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 Oxidation and Reduction
Oxidative Cleavage of Alkenes with KMnO4:
• Addition of conc. KMnO4 in base with heat to an alkene results in
cleavage between the carbons of the double bond.
• Products depend on the number of hydrogens attached to each
carbon of the alkene. Look at each C.

• R-CH=CH2 One H on C yields a carboxylic acid, RCOOH

Two Hs on C yields carbon dioxide, CO 2

• R-CH=CH-R' One H on C yields a carboxylic acid, RCOOH +

R'COOH
• R2-C=CH2 No Hs on C yields a ketone, R-CO-R
Two Hs on C yields carbon dioxide, CO 2

31
 Oxidation and Reduction
Oxidative Cleavage of Alkenes with O3:
• Oxidative cleavage of an alkene breaks both the  and  bonds of
the double bond to form two carbonyl compounds. Cleavage with
ozone (O3) is called ozonolysis.

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 Oxidation and Reduction
Oxidative Cleavage of Alkenes with O3:
• Addition of O3 to the  bond of an alkene forms an unstable
intermediate called a molozonide, which rearranges to an ozonide
in a stepwise process.
• The unstable ozonide is reduced to afford carbonyl compounds. Zn
(in H2O) or dimethylsulfide (CH3SCH3) are two common reagents
used to convert the ozonide into carbonyl compounds.

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 Oxidation and Reduction
Oxidative Cleavage of Alkenes with O3:
• Ozonolysis of dienes or other polyenes results in oxidative cleavage
of all C=C bonds.
• It is important to note that when oxidative cleavage involves a
double bond that is part of a ring, the ring opens up affording a
single chain with two carbonyls at the carbons where the double
bonds were originally.

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 Oxidation and Reduction
Oxidative Cleavage of Alkynes with O3:
• Alkynes undergo oxidative cleavage of the  and both  bonds.
• Internal alkynes are oxidized to carboxylic acids (RCOOH).
• Terminal alkynes afford a carboxylic acid and CO2 from the sp
hybridized C—H bond.

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 Oxidation and Reduction
Oxidation of Alcohols:
• Alcohols are oxidized to a variety of carbonyl compounds.

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 Oxidation and Reduction
Oxidation of Alcohols:
• Recall that the oxidation of alcohols to carbonyl compounds is
typically carried out with Cr6+ oxidants, which are reduced to Cr4+
then to Cr3+ products.
• CrO3, Na2Cr2O7, and K2Cr2O7 are strong, nonselective oxidants
used in aqueous acid (H2SO4 + H2O).
• PCC is soluble in CH2Cl2 (dichloromethane) and can be used
without strong acid present, making it a more selective, milder
oxidant.

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 Oxidation and Reduction
Oxidation of 2° Alcohols:
• Any of the Cr6+ oxidants effectively oxidize 2° alcohols to
ketones.

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 Oxidation and Reduction
Oxidation of 1° Alcohols:
• 1° Alcohols are oxidized to either aldehydes or carboxylic
acids, depending on the reagent.

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 Oxidation and Reduction
Oxidation of 1° Alcohols:

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 Oxidation and Reduction
Oxidation of 1° Alcohols:

• Cr6+ oxidations are characterized by a color change.

The red-orange Cr6+ reagent is reduced to the green
Cr3+.

• Some devices used to measure blood alcohol content

make use of this color change: Oxidation of
CH3CH2OH, the 1° alcohol in alcoholic beverages,
with orange K2Cr2O7 forms CH3COOH and green
Cr3+.

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 Oxidation and Reduction
Oxidation of 1° Alcohols:

• Blood alcohol level can be determined by having an

individual blow into a tube containing K2Cr2O7,
H2SO4, and an inert solid.

• The higher the concentration of CH3CH2OH in the

breath, the more Cr6+ is reduced, and the farther the
green Cr3+ color extends down the length of the
sample tube.

• The extent of the green color is then correlated with

blood alcohol levels.
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 Oxidation and Reduction
Oxidation of 1° Alcohols:
Figure 12.10 Blood
alcohol screening

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 Oxidation and Reduction
Green Chemistry:
• Green chemistry is the use of environmentally safe or harmless
methods to synthesize compounds.
• Its purpose is to use safer reagents and less solvent, and develop
reactions that form fewer by-products and generate less waste.
• Since many oxidation methods use toxic reagents (such as OsO 4
and O3) and corrosive acids such as H2SO4, or generate
carcinogenic by-products (such as Cr3+), alternative less
problematic regents have been developed.
One methods uses a polymer supported Cr3+ reagent, Amberlyst
A-26 resin-HCrO4, this avoids the use of strong acid, and forms a
Cr3+ by-product that can easily be removed from the product by
filtration.
The Amberlyst A-26 resin consists of a complex hydrocarbon
network with cationic ammonium ion appendages that serve as
counterions to the anionic chromium agent, HCrO4¯.
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 Oxidation and Reduction
Green Chemistry:
• Heating the insoluble polymeric reagent with an alcohol
results in oxidation to a carbonyl compound, with formation
of an insoluble Cr3+ by-product which can be regenerated
and reused in a subsequent reaction.

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 Oxidation and Reduction
Green Chemistry:

• With Amberlyst A-26 resin-HCrO4¯, 1° alcohols are

oxidized to aldehydes and 2° alcohols are oxidized to
ketones.

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 Oxidation and Reduction

The Sharpless Epoxidation of allylic alcohols:

• Recall that in the reactions we have discussed thus far, an

achiral starting material has reacted with an achiral reagent
to give either an achiral product, or a racemic mixture of
two enantiomers.

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 Oxidation and Reduction
The Sharpless Epoxidation:
• The Sharpless reagent consists of three different components:
tert-butylhydroperoxide (CH3)3COOH; a titanium catalyst (usually
titanium(IV) isopropoxide), Ti[OCH(CH3)2]4; and diethyl tartrate
(DET).
• There are two different chiral diethyl tartrate isomers, labeled as
(+)-DET or (-)-DET to indicate the direction in which they rotate
plane polarized light.
• The identity of the DET isomer determines which enantiomer is
the major product obtained in the epoxidation.

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 Oxidation and Reduction
The Sharpless Epoxidation:

• In the Sharpless epoxidation, the double bonds of

allylic alcohols are oxidized to epoxides.

• Since the formation of only one enantiomer is

favored, the reaction is said to be enantioselective
or asymmetric.

• An enantioselective reaction affords predominantly

or exclusively one enantiomer.

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 Oxidation and Reduction
The Sharpless Epoxidation:
• The peroxide is the oxidizing agent (1:1 with the
alkene). The titanium and DET form a catalytic
complex (about 5-10%).

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 Oxidation and Reduction
The Sharpless Epoxidation:
• To determine which enantiomer is formed from a given
isomer of DET, draw the allylic alcohol in a plane, with the
OH group in the bottom right hand corner; then note that:

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 Oxidation and Reduction
The Sharpless Epoxidation:

• Reactions [1] and [2] are highly enantioselective as each

has an enantiomeric excess of 95% (i.e., 97.5% of the
major enantiomer and 2.5% of the minor enantiomer).
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 Thiols (Mercaptans)
• Sulfur analogues of alcohols are called thiols.
• The —SH group is called a mercapto group.
• Named by adding the suffix -thiol to the alkane
name.
• They are commonly made by an SN2 reaction
so primary alkyl halides work better.

Chapter 10 53
 Synthesis of Thiols

• The thiolate will attack the carbon displacing the

halide.
• This is an SN2 reaction so methyl halides will
react faster than primary alkyl halides.
• To prevent dialylation use a large excess of
sodium hydrosulfide with the alkyl halide.
Chapter 10 54
 Thiol Oxidation

Thiols can be oxidized to form disulfides. The disulfide bond

can be reduced back to the thiols with a reducing agent.
Chapter 10 55